Evidence map›Paper›PMID 37569721›Full record

ArticleInternational journal of molecular sciences2023

Sortilin Is Upregulated in Osteoarthritis-Dependent Cartilage Calcification and Associated with Cellular Senescence.

Elisabeth Richter, Christoph H Lohmann, Francesco Dell'Accio, Claudia Goettsch, Jessica Bertrand

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Sortilin and its potential role in cardiovascular pathology.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Elisabeth RichterDepartment of Orthopaedic Surgery, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany.
Christoph H LohmannDepartment of Orthopaedic Surgery, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany.ORCID 0000-0002-2962-2183
Francesco Dell'AccioWilliam Harvey Research Institute, Queen Mary University London, London EC1M 6BQ, UK.
Claudia GoettschDepartment of Internal Medicine I-Cardiology, RWTH Aachen University, 52062 Aachen, Germany.ORCID 0000-0002-7973-1329
Jessica BertrandDepartment of Orthopaedic Surgery, Otto von Guericke University Magdeburg, 39120 Magdeburg, Germany.ORCID 0000-0001-9511-4999
Otto-von-Guericke-Universität Magdeburg · DERWTH Aachen University · DEWilliam Harvey Research Institute · GB

Funding

Deutsche Forschungsgemeinschaft DFG BE 4328/9-1
6 · The paper itself

Abstract

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage calcification, loss of articular cartilage, bone changes, pain, and disability. Cartilage calcification is one hallmark of OA and is predominantly caused by basic calcium crystals formed due to an imbalance of the pyrophosphate pathway. Sortilin is a transmembrane protein that contributes to vascular calcification in atherosclerosis by externalizing alkaline phosphatase (ALP)-containing vesicles. Calcification in atherosclerosis and osteoarthritis has been associated with cellular senescence. The aim of this study was to investigate the potential role of sortilin and senescence in osteoarthritis-dependent cartilage calcification. Osteoarthritic cartilage from human knee joints was collected after joint replacement, and samples were analyzed by immunohistochemistry and quantitative RT-PCR analysis. Human chondrocytes were treated with osteogenic medium for up to 21 days to induce calcification. Western blots for sortilin and ALP, as well as an ALP activity assay, were performed. Human chondrocytes were treated with mitomycin C to induce senescence, and sortilin expression was quantified at the protein and gene levels. Sections of knee joints from a murine model of osteoarthritis were stained for sortilin and p16 and analyzed by immunohistochemistry. Treatment of wild-type chondrocytes using an osteogenic medium similar to human chondrocytes was performed. Osteoarthritic cartilage from mouse and human knee joints showed an increased number of sortilin and p16-positive chondrocytes compared to healthy cartilage. This observation was corroborated by increased gene expression of sortilin and p16 in mild and moderate osteoarthritic cartilage samples. To investigate the mechanism of sortilin regulation, human chondrocytes were treated with osteogenic medium to induce calcification. Sortilin protein levels and expression were increased after 7 days of stimulation, whereas ALP levels and activity were upregulated after 21 days of stimulation. Similar observations were made in a murine osteoarthritis model. Mechanistically, senescent chondrocytes induced by mitomycin C showed an upregulation of sortilin and ALP gene expression compared to non-senescent chondrocytes. Our data indicate that sortilin and ALP are upregulated during cartilage calcification, which is associated with chondrocyte senescence and thus might contribute to the pathogenesis of osteoarthritis. Cellular senescence seems to induce sortilin expression.

Indexed as

Adaptor Proteins, Vesicular TransportCalcinosisCartilage, ArticularCellular SenescenceOsteoarthritisAgedAnimalsCells, CulturedChondrocytesFemaleHumansMaleMiceMice, Inbred C57BLMiddle AgedUp-RegulationAdaptor Proteins, Vesicular Transportcalcificationcartilagechondrocytesosteoarthritissenescencesortilin

Identifiers

PMID37569721
PMCPMC10418692
OpenAlexW4385491773

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.